biostudies-literatureKrisai PSwiss National Science Foundation120https://www.ebi.ac.uk/biostudies/studies/S-EPMC12916941biostudies-literatureUnknown6(1)<h4>Background</h4>The interrelationships between atrial fibrillation (AF), brain lesions and cognitive function are poorly understood. We aimed to investigate the relationship of AF with brain lesions and cognition.<h4>Methods</h4>We enrolled 1,480 patients with and 959 without AF in a multicenter prospective study (Swiss-AF; NCT02105844). We assessed brain structure, and cognition using the Montreal Cognitive Assessment (MoCA). Brain magnetic resonance imaging (MRI) was performed to assess large non-cortical and cortical infarcts (LNCCI), small non-cortical infarcts (SNCI), white matter hyperintensities (WMH), and microbleeds. Using causal mediation analyses, we investigated the direct (lesion-independent) and indirect (lesion-mediated) effects of AF on cognition.<h4>Results</h4>Mean ageCommunications medicineIschemic brain infarcts, white matter hyperintensities, and cognitive impairment are increased in patients with Atrial Fibrillation.PMC12916941148474Ruckli-Kaeppeli AFrangi-Kultalahti JHurbin MAnesini AGret AConen DShah DMonsch AGallet HHuber PFirmann MGasser ALoewe AVicari LRodondi NCereda CFischer UMelchiorre PAMCoslovsky MRigamonti EBrenner REberli FNadler JRommers NDahlheim LMonsch AUDillier RBuhler KKuest SSchmid RSchwab NNovak JBernheim ABadertscher PScheuch KYoung MStagliano SGemperle MLazeyras FDuering MMeier SRoth MMeier VRoth JKuhne MTynan NStephan FPSchlomowitsch FVillinger JSporns PAeschbacher SLiedtke CTerrot TAltermatt AHennings ESchneider CFluckiger TConte GBonetti NLaube EBaumann CMeier JMehmann BEhret GRegoli FJuchli IKellner-Weldon FFrick MSchneider XHellrigl SFink KGallino AOsswald SBonati LHJadidi AGuillermet ESticherling CFeller MJusti VAmmann PRuberte ECaputo MLBerte BRime MFoucras SBeer JHRoten LGrau AJung SAltmann DSinnecker TSimon PAdam LPerret PValentino MDDi Valentino MSchwenkglenks MAubert CEKobza RSchmidt KRonchi MReichlin TWiederkehr CKoch MPorretta APMuller ASPeronaci RPaladini RERutz FRuckstuhl NZuern CSRussi ITavel PLauriers NMeyre PBDeubelbeiss MObst TAebersold HMahfoud FSaffari THZKerler RThoni AZuber VZuber PAujesky DFoster FGirroy CWenger RWeishaupt DLeuenberger SRakovic DMuller AMuller CSchlapfer JVollmin GAuricchio ACianfoni APeter RMoutzouri EDuring MNuoffer ANeuschwander PHofer DStuderus KJeger RFriedli CSchweigler APin AMurugiah SDe Perna MLLovblad KOCarmine DWurfel JMoschovitis GHischier DFranzini CEhrsam LMeyer-Zurn CKrisai PeMBA, for the Swiss-AF InvestigatorsFuhrer JMattle HHayoz DCamporini CMean MVitelli SNetzer SSalzmann SBlum SAmann MGroen CfalseIschemic brain infarcts, white matter hyperintensities, and cognitive impairment are increased in patients with Atrial Fibrillation.<h4>Background</h4>The interrelationships between atrial fibrillation (AF), brain lesions and cognitive function are poorly understood. We aimed to investigate the relationship of AF with brain lesions and cognition.<h4>Methods</h4>We enrolled 1,480 patients with and 959 without AF in a multicenter prospective study (Swiss-AF; NCT02105844). We assessed brain structure, and cognition using the Montreal Cognitive Assessment (MoCA). Brain magnetic resonance imaging (MRI) was performed to assess large non-cortical and cortical infarcts (LNCCI), small non-cortical infarcts (SNCI), white matter hyperintensities (WMH), and microbleeds. Using causal mediation analyses, we investigated the direct (lesion-independent) and indirect (lesion-mediated) effects of AF on cognition.<h4>Results</h4>Mean age2026-01-01T00:00:00Z2026 Jan2026-07-16T10:02:42.675Z2026-07-09T10:48:12.653ZS-EPMC129169414159321710.1038/s43856-026-01389-w